title: Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP).
abstract: The clinical presentation of thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies (TMAs) can often be similar. The role of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in diagnosing TTP is accepted by most researchers but continues to be debated in a few studies. We report the experience of our single-centre academic institution, where ADAMTS13 is used to diagnose TTP and guide plasma exchange (PLEX). Patients presenting to our institution with thrombotic microangiopathy (60 patients) between January 2006 and December 2012 were divided into two groups based on ADAMTS13 activity and clinical history. Patients with ADAMTS13 activity <10% were included in the TTP (n = 30) cohort while patients with activity >11% were classified as 'other microangiopathies' (TMA, n = 30). PLEX was only initiated in patients with a high likelihood of TTP and discontinued when the baseline ADAMTS13 activity was >11%. Patients with severe ADAMTS13 deficiency (TTP group) showed significant presenting differences: lower platelet counts, less renal dysfunction, higher presence of neurological abnormalities, and greater haemolysis markers as compared to non-deficient patients (TMA group). Most importantly, patients without severe ADAMTS13 deficiency were safely managed without increased mortality despite receiving no PLEX or discontinuing PLEX after a short course (upon availability of ADAMTS13 results). In conclusion, ADAMTS13 can be used to diagnose TTP and guide appropriate PLEX therapy.
authors.affiliation: Department of Pathology, Division of Transfusion Medicine and Hemostasis, Dallas, TX, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Shah
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rutherford
authors.forename: Karen
authors.initials: K
authors.lastname: Matevosyan
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Shen
authors.forename: Ravi
authors.initials: R
authors.lastname: Sarode
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D002648:Child; D003937:Diagnosis, Differential; D019468:Disease Management; D005260:Female; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000172:deficiency; D008875:Middle Aged; D010951:Plasma Exchange / Q000379:methods; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy; D012189:Retrospective Studies; D000069283:Rituximab; D057049:Thrombotic Microangiopathies / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; atypical haemolytic uremic syndrome; plasma exchange; thrombotic microangiopathy; thrombotic thrombocytopenic purpura